Mouse epidermal cell cultures will be used to study carcinogenesis in vitro and by combined in vitro and in vivo techniques. The role of state of differentiation, proliferative capacity and cell cycle will be studied. Phorbol ester will be added to initiated cells to study promotion in vitro. Vitamin A can alter epidermal cell differentiation in vitro. The role of Vitamin A in carcinogenesis will be studied in this system. An attempt will be made to separate effects on initiation from effects on promotion. Parallel in vivo studies will be performed. The interaction of chemical carcinogens with informational subunits of the cell will be studied using isolated chromosomes and nucleic acids. Attempts will be made to identify specific areas of interactions within the mammalian genome.